First-Dose Pharmacokinetics of Lithium Carbonate in Children and Adolescents

Abstract

This study examines the pharmacokinetics of oral doses of lithium carbonate immediate-release capsules after administration of 600 or 900 mg in children and adolescents with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, bipolar I disorder. Lithium plasma concentrations were followed over 48 to 72 hours in 39 subjects (20 male and 19 female subjects; ages, 7-17 years) with mixed or manic episodes enrolled at 7 clinical sites participating in the Collaborative Lithium Trials. Population pharmacokinetic modeling was performed using NONMEM, and influences of patient covariates on pharmacokinetics parameters were examined. The pharmacokinetics of lithium was best described using a 2-compartment model with a lag time and first-order absorption. There was considerable variability in lithium exposures. Lithium clearance related best to fat-free mass. Inclusion of fat-free mass as a covariate reduced the between-subject variability from 52% to 42%. Lithium clearances did not vary systematically with age group, dose, sex, or creatinine clearances. Allometrically scaled clearance and volume of distribution from the population analysis were within the range reported in adults. Single-dose profiles of lithium in young patients with BP-1 show marked variability. Therefore, ongoing serum monitoring is needed during continued therapy. The developed population pharmacokinetic model may be used to predict other dosage regimens, support scaling from adult to pediatric pharmacokinetics, and support the design of future clinical trials.

Lithium in the Acute Treatment of Bipolar I Disorder: A Double-Blind, Placebo-Controlled Study

“…17,18 The starting dose of lithium (supplied as 300-mg, regular-release capsules) was either 600 or 900 mg/d. Participants weighing ,30 kg started with 600 mg/d; all other participants began lithium therapy with 900 mg/d.…”

“…After establishing the pharmacokinetics, the empirically determined dosing strategy, and tolerability through an initial set of studies, 17,18 the first randomized, double-blind, placebocontrolled lithium acute efficacy trial was conducted in a different patient sample. The present article describes the key findings of that trial and the impact the results may have on pediatric mental health.…”

Bipolar Disorder in 10–17 Year Old Patients: Treatment Options and Cautions

“…Its half-life elimination is lower in children as its total renal clearance is higher. 41 Recurrent follow-up during initial titration is necessary to ensure that blood concentrations are within a therapeutic and safe range, because of Li's narrow therapeutic index. The recommended levels are 0.8-1.2 mEq/L for maintenance therapy and 1.0-1.5 mEq/L for an acute manic episode, even though these levels are based on studies of adults with BD.…”

CoLT and TEAM: What Do the Results Tell Clinicians about Rational Treatment for Pediatric Bipolar Disorder?

“…Participants were diagnosed with BP-I in a manic or mixed state using the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Episode (K-SADS-PL) and had a Young Mania Rating Scale (YMRS) score of ≥20, along with other criteria as outlined by Findling and colleagues (Findling et al, 2008). Study 1 completed its data collection and released some findings on the first phase of the study (Findling et al, 2011;Findling et al, 2010). Study 2 is in the process of data collection, still actively enrolling participants at this time.…”